[Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment].

Objective: To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis (P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods: A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 µg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results: At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1ß [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm2), the thickness of the esophageal wall (median 172.52 µm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1ß [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions: P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Oral sulfate solution versus polyethylene glycol for bowel preparation before colonoscopy, meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: This study aimed to compare oral sulfate solution (OSS) with polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: A literature search was performed on PubMed, Ovid, and Cochrane Databases for randomized clinical trials (RCT) comparing OSS with PEG for bowel preparation before colonoscopy. The last search was performed on 22 August 2023. The primary outcome was the quality of bowel preparation. The outcomes were compared by meta-analysis and trial sequential analysis (TSA). RESULTS: A total of 14 RCTs with 4526 patients were included. OSS was comparable with PEG regarding adequate bowel preparation [P = 0.16, odds ratio (OR) = 1.19, 95% confidence interval (CI) [0.93, 1.51], I2 = 0%]. However, OSS showed obvious priority in excellent bowel preparation (P < 0.001, OR = 1.62, 95% CI [1.27, 2.05], I2 = 0%) and total Boston bowel preparation scale (BBPS) [P = 0.02, weighted mean difference (WMD) = 0.27, 95% CI [0.05, 0.50], I2 = 84%]. Additionally, the detection rate of polyps (P = 0.001, OR = 1.44, 95% CI [1.15, 1.80], I2 = 0%) and adenoma (P = 0.007, OR = 1.22, 95% CI [1.06, 1.42], I2 = 0%) was significantly higher in the OSS group. The two groups showed comparable incidence of adverse events except for a higher incidence of dizziness (P = 0.02, OR = 1.74, 95% CI [1.08, 2.83], I2 = 11%) was indicated in the OSS group. Moreover, OSS was associated with a higher satisfaction score (P = 0.02, WMD = 0.62, 95% CI [0.09, 1.15], I2 = 70%). In the TSA, the cumulative Z-curve crossed both the conventional boundary and trial sequential monitoring boundary and the required information size has been reached for excellent bowel preparation and total BBPS. CONCLUSION: The current data demonstrated that OSS was associated with better quality of bowel preparation. More clinical trials are still needed to confirm other outcomes.

Brain targeting efficacy of novel drug delivery system in the treatment of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group. MATERIALS AND METHODS: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration. RESULTS: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration. CONCLUSIONS: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.

Allicin in pregnancy diets modulates steroid metabolism in pregnant sows and placental sulphate metabolism promoting placental angiogenesis and foetal development.

The low-birth-weight of piglets is an important factor affecting pig enterprises. The placenta, as a key organ for material exchange between mother and foetus, directly influences the growth and development of the foetus. Allicin exhibits various biological activities, including anti-inflammatory and antioxidant properties. It may also play a crucial role in enhancing sow reproductive performance and placental angiogenesis. In this study, we used 70 lactating Landrace × Yorkshire binary heterozygous sows to explore the effect of allicin on the reproductive performance of sows and placental development. The sows were randomly assigned into the Allicin group (Allicin), which was fed with a diet containing 0.25% allicin, and the negative control group, which was fed with basal feed. The experimental period lasted for 114 d from the date of mating to the end of farrowing. The results showed that the addition of allicin to the gestation diets increased the number of total born piglets, born alive piglets, and high-birth-weight piglets, reduced peripartum oxidative stress, alleviated dysregulation of glucose-lipid metabolism in sows, and increased the levels of antioxidant markers in the placenta. Differential analysis of metabolites in maternal plasma and placenta samples by non-targeted metabolomics revealed that allicin improved cholesterol metabolism, steroid biosynthesis, and increased plasma progesterone levels in sows. Allicin promoted sulphur metabolism, cysteine and methionine metabolism in placental samples and increased the hydrogen sulphide (H2S) content in the placenta. In addition, Quantitative Real-time PCR, Western blot and immunofluorescence results showed that allicin upregulated the expression of angiogenesis-related genes, VEGF-A, FLK 1 and Ang 1, in the placenta, implying that it promoted placental angiogenesis. These results indicate that supplementing the diet of pregnant sows with allicin reduces oxidative stress, alleviates dysregulation of glucose-lipid metabolism during the periparturient period, and promotes placental angiogenesis and foetal development by increasing plasma progesterone level and placental H2S content.

Association between Cerebrospinal Fluid sTREM2 Levels and Depression: The Alzheimer's Disease Neuroimaging Initiative Study.

OBJECTIVE: Previous studies demonstrated a significant protective effect of elevated cerebrospinal fluid (CSF) sTREM2 levels on brain structure and cognitive decline. Nonetheless, the role of sTREM2 in the depression progression remains unclear. This study aimed to investigate the association between CSF sTREM2 levels and longitudinal trajectories of depression. METHODS: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study were used. CSF sTREM2 levels and depression were measured using an ELISA-based assay and the Geriatric Depression Scale (GDS-15), respectively. Linear mixed-effect models were employed to assess the relationships between CSF sTREM2 levels and GDS scores. RESULTS: A total of 1,017 participants were enrolled at baseline, with a mean follow-up time of 4.65 years. Baseline CSF sTREM2 levels were negatively correlated with GDS scores (ß=-0.21, P=0.022) after adjustment for age, gender, race/ethnicity, education, APOE ε4 carrier status, TREM2 rare variant carrier status, marital status, smoking, and clinical cognitive status. CONCLUSION: Our findings suggested that a higher level of CSF sTREM2 was associated with a lower risk of depression.

[Influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy].

Objective: To evaluate the influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy. Methods: Clinical data of 38 children who underwent hemispherectomy from January 1, 2011 to October 31, 2023 at Xuanwu Hospital of Capital Medical University were retrospective collected. Patients were divided into study group (n=17) and control group (n=21) according to whether thromboelastography was employed to guide hemostatic algorithm. Demographic data and surgical data were recorded. The primary outcomes were allogeneic transfusion rates, including RBC transfusion rate, plasma transfusion rate, and platelets transfusion rate. The second outcomes were estimated blood loss, postoperative seizures during hospitalization, thromboembolic events, and length of hospital stay. Results: There were 13 boys and 4 girls with mean age of (5.7±3.3) years old in study group, and 16 boys and 5 girls with mean age of (7.4±3.4) years old in control group. The surgery duration, anesthesia duration and the proportion of prophylactic administration of tranexamic acid in study group were (424.5±98.5) min, (542.8±106.9) min, and 94.1% (16/17), which were higher than (353.1±85.3) min, (445.3±87.9) min, and 47.6% (10/21) in control group (all P<0.05). The rates of intra- and perioperative allogeneic plasma transfusion in study group were 52.9% (9/17) and 64.7% (11/17) respectively, which were lower than 90.5% (19/21) and 95.2% (20/21) in control group (all P<0.05). The ratio of fibrinogen concentrates administration in study group was 58.8% (10/17), which was higher than that in control group [4.8% (1/21), P=0.001]. There were no statistically differences in intra- and perioperative allogeneic RBC transfusion rates between the two groups (all P>0.05). No platelets were transfused in both groups. There were no statistically differences in estimated blood loss, postoperative seizures during hospitalization and the length of hospital stay between the two groups (all P>0.05). No postoperative thromboembolic events were observed. Conclusion: Thromboelastography-guided hemostatic algorithm can reduce allogeneic plasma transfusion requirements but not RBC transfusion requirements during pediatric hemispherectomy.

[Analysis of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma].

Objectives: To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma. Methods: A retrospective analysis was performed on clinical and pathological data of 15 patients misdiagnosed as branchiogenic carcinoma at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2000 and December 2020. Results: Among the 15 patients, 6 were nasopharyngeal squamous cell carcinoma, 4 tonsil squamous cell carcinoma, 2 tongue root squamous cell carcinoma, 2 hypopharyngeal squamous cell carcinoma and 1 thyroid papillary carcinoma. The median time from the diagnosis of branchial cleft carcinoma to the discovery of primary lesions was 3.58 months (0-76 months). The causes of misdiagnosis might be the lack of experience in the diagnosis and treatment of branchial cleft carcinoma, and not enough attention to comprehensive examination and close follow-up. Conclusions: Different from oropharyngeal cancer reported internationally, the proportion of misdiagnosed cases with nasopharyngeal carcinoma as the primary site in the current article is higher. As a country with a high incidence of nasopharyngeal carcinoma, the examination of nasopharynx should not be taken lightly. Most hidden cases can be found in the comprehensive examination in a short time, while a few cases need long-term follow-up. Finding the primary sites should not rely too much on imaging examination, and we cannot ignore the importance of clinical physical examination.

[Interpretation of Chinese guideline for the clinical management of patients with unruptured intracranial aneurysms (2024)].

With the popularization of cerebrovascular imaging technology, the clinical detection rate of unruptured intracranial aneurysm (UIA) is increasing. UIA has a low risk of rupture, but once ruptured, it can seriously affect human health. The treatment of UIA is highly controversial and has attracted widespread clinical attention. The Society of Neurosurgery of the Chinese Medical Association, the Society of Cerebrovascular Surgery of the Chinese Stroke Association, the National Center for Neurological Diseases, and the National Center for Clinical Research on Neurological Diseases jointly formulate "Chinese guideline for the clinical management of patients with unruptured intracranial aneurysm management (2024)", which adopts a modular format, highlighting management recommendations and indicating current research deficiencies and future research directions. It provides comprehensive clinical management recommendations on UIA epidemiology, population screening, clinical imaging and diagnosis, rupture risk assessment, treatment decisions and choices, postoperative follow-up, and long-term management. The evidence sources are divided into the Chinese population and other populations, which helps guide clinical practice in China.

[Treatment strategy for low-risk papillary thyroid carcinoma with diameter smaller than 1 cm: immediate surgery vs active surveillance].

The incidence of differentiated thyroid cancer is increasing rapidly worldwide, with subcentimeter papillary thyroid carcinoma (SPTC) with a diameter of less than 1 cm accounting for more than 50%. Active surveillance (AS) as an alternative to immediate surgery for low-risk SPTC was launched in Japan in the 1990s and has been implemented in several countries, including Japan and the United States. However, the indications and safety of performing AS for low-risk SPTC remain controversial. In this article, the author summarizes the existing literature and explores its limitations of AS implementation, the effectiveness of surgical treatment, and the different attitudes of countries on AS, aiming to provide some references for the treatment options of low-risk SPTC.

[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Application of seamless phase â ¡/â ¢ design in vaccine clinical trials].

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

[Discussion on pathological diagnosis of vascular diseases based on ISSVA classification].

The diagnosis of vascular diseases is not only about distinguishing neoplastic or non-neoplastic lesions, but also focusing more on emphasizing the essence of the disease, namely the presence or absence of endothelial cell proliferation, and further to distinguishing true hemangioma tumors or vascular malformation. This article is based on the International Society for the Study of Vascular Anomalies (ISSVA) classification, which is widely used in clinical practice, and discusses the related pathological diagnosis issues of vascular diseases.

[Clinicopathological and genetic characteristics of common lymphatic malformations in superficial soft tissues].

Objective: To investigate the clinicopathological features, classification, and genetic characteristics of common lymphatic malformation (CLM) in superficial soft tissue. Methods: A retrospective study of 110 patients with the diagnosis of CLM at the Henan Province People's Hospital, China from August 2019 to August 2022 was performed. The clinicopathological features, relevant immunohistochemical (IHC) staining results, and fluorescence quantitative PCR of PIK3CA mutation were analyzed, and patients were followed up. Results: Among the 110 CLM patients, there were 53 males and 57 females; 65 cases (65/110, 59.1%) were first detected when the patients were≤2 years old. The most common location was the head and neck in 41 cases (41/110, 37.3%). Clinically, 102 cases (102/110, 92.7%) were solitary, 83 cases (83/110, 75.5%) were skin-colored, 69 cases (69/110, 62.7%) had indistinct borders, and 10 cases (10/110, 9.1%) had diffuse and severe macroscopic manifestations. There were 52 macrocystic type (52/110, 47.3%), 23 microcystic type (23/110, 20.9%), and 35 combined type (35/110, 31.8%). The macrocystic CLM presented as soft, translucent masses with large cystic cavities on the cut surface, and histologically they were composed of large, irregularly dilated channels that were thicker with irregular smooth muscle and lymphocytic infiltration. Microcystic CLM showed wartlike projections or translucent blisters on the skin, with small honeycomb structures on the cut surface, and histologically consisted of round or angular dilated small lymphatic vessels with little or no smooth muscle. The combined CLM had both macrocystic and microcystic morphologies. IHC staining showed that the lymphatic endothelial cells were positive for LYVE-1, D2-40, PROX1, CD31, and VEGFR3 but negative for CD34; in the macrocystic and combined CLM vessel walls were positive for SMA. Eight of 13 CLM had PIK3CA mutation. All patients were followed up, and 24 (24/110, 21.8%) had relapses, which more frequently occurred in combined type, followed by microcystic type. Conclusions: CLM is a congenital vascular malformation composed of dilated, abnormal lymphatic channels, with PIK3CA mutation. There are significant differences in clinicopathological characteristics among the different types. Since microcystic and combined CLM are prone to recurrence, accurate pathological subtyping is necessary to guide treatment and to predict prognosis.

[Application of uniportal video-assisted thoracoscopic surgery in the treatment of tuberculous destroyed lung].

Objective: To examine the efficacy of uniportal video-assisted thoracoscopic surgery in the treatment of tuberculous destroyed lung. Methods: This is a retrospective case series study. The clinical data of 33 patients with tuberculous destroyed lung who had received uniportal video-assisted thoracoscopic pulmonary resection from June 2020 to May 2022 in Department of Surgery, Wuhan Pulmonary Hospital were retrospectively analyzed. There were 13 males and 20 females, aged (47.5±16.2) years (range: 19 to 68 years). The course of the disease was from 15 days to 8 years. All 33 cases had pleural adhesions, including 30 cases with total pleural adhesions and atresia. There were 21 cases of calcification of the thoracic lymph node, 17 cases of aspergillus infection, 4 cases of drug-resistant tuberculosis. The surgical incision was located at the midline of the fifth intercostal axilla, length 4 to 5 cm. The principle of separating pleural adhesions was easy first and difficult later, and then appropriate procedures were selected to resect the diseased lung based on the exploration situation. There were 12 cases that underwent superior lobectomy, 11 cases that underwent superior lobectomy and dorsal segmentectomy, 3 cases that underwent inferior lobectomy, 3 cases that underwent pneumonectomy, 2 cases that underwent middle and inferior lobectomy, and 1 case that underwent superior lobectomy, dorsal segmentectomy and basal segment wedgectomy. The surgical techniques, perioperative evaluation and treatment, management of complications, and the outcome were summarized. Results: Six cases were converted to thoracoscope assisted small incision or thoracotomy. For 27 cases who successfully underwent uniportal VATS, the operation time was (238.7±76.8) minutes (range: 60 to 420 minutes), the intraoperative bleeding was (400.4±315.9) ml (range: 50 to 1 200 ml). The duration of postoperative drainage was (12.7±8.3) days (range: 3 to 42 days). The postoperative hospital stay was (15.2±7.9) days (range: 6 to 43 days). Persistent postoperative pulmonary leakage occurred in 12 cases. There were 2 cases of active thoracic bleeding, one of which was cured with conservative treatment. The other case underwent secondary operation. One case of bronchopleural fistula was cured after continuous thoracic drainage to control infection and implantation of one-way bronchial valve through a fiberoptic bronchoscope. Conclusion: For selected patients with tuberculous destroyed lung, choosing the reasonable surgical procedures and techniques, the uniportal VATS could reduce surgical trauma.

[Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

Sleeve gastrectomy links the attenuation of diabetic kidney disease to the inhibition of renal tubular ferroptosis through down-regulating TGF-ß1/Smad3 signaling pathway.

PURPOSE: To investigate how sleeve gastrectomy (SG), a typical operation of bariatric surgery, attenuated symptom, and progression of diabetic kidney disease (DKD). METHODS: DKD model was induced by high-fat diet (HFD) combined with streptozocin in Wistar rats. SG was performed, and the group subjected to sham surgery served as control. The animals were euthanized 12 weeks after surgery, followed by sample collection for the subsequent experiment. The HK-2, a renal proximal tubular epithelial cell line derived from human, was utilized to investigate the potential mechanisms. RESULTS: SG improved metabolic parameters and glucose homeostasis, and could alleviate DKD in terms of renal function indices as well as histological and morphological structures in DM rats, accompanied with a significant reduction in renal tubular injury. Compared with sham group, SG reduced the renal tubular ferroptosis. To further clarify the mechanism involved, in vitro experiments were performed. In the presence of high glucose, renal tubular TGF-ß1 secretion was significantly increased in HK-2 cell line, which led to activation of ferroptosis through TGF-ß1/Smad3 signaling pathway. Inhibition of TGF-ß1 receptor and phosphorylation of Smad3 significantly ameliorated TGF-ß1-mediated ferroptosis. In vivo experiments also found that SG improved the hyperglycemic environment, reduced renal TGF-ß1 concentrations, and down-regulated the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: With the capacity to lower the glucose, SG could attenuate the ferroptosis by inhibiting TGF-ß1/Smad3 signaling pathway in DKD rats, and eventually attenuated DKD.